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Pharmacogenetic analysis of adjuvant FOLFOX for Korean patients with colon cancer

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Abstract

Purpose

Ethnic diversity of genetic polymorphism can result in individual differences in the efficacy and toxicity of cancer chemotherapy.

Methods

We analyzed 20 germline polymorphisms in 10 genes (TS, MTHFR, ERCC1, XPD, XRCC1, ABCC2, AGXT, GSTP1, GSTT1 and GSTM1) from prospectively enrolled 292 Korean patients treated with adjuvant oxaliplatin plus leucovorin plus 5-fluorouracil (FOLFOX) for colon cancer.

Results

In contrast to previous studies in Caucasians, neutropenia (grade 3–4, 60.5 %) was frequently observed, whereas only 16.4 % experienced grade 2 or more sensory neuropathy. Neutropenia was more frequent in MTHFR 677TT [adjusted odds ratio (OR) 2.32, 95 % confidence interval (CI) 1.19–4.55] and ERCC1 19007TT (adjusted OR 4.58, 95 % CI 1.20–17.40) genotypes. Patients harboring XRCC1 23885GG experienced less grade 2–4 neuropathy [adjusted OR 0.52, 95 % CI 0.27–0.99]. MTHFR 677TT (p = 0.002) and XRCC1 23885GG (p = 0.146) genotypes were also more prevalent in Koreans compared to Caucasians. TS ‘low’ genotype (adjusted HR 1.83, 95 % CI 1.003–3.34) was significantly related to shorter disease-free survival. Overall survival was not significantly different according to the polymorphisms.

Conclusions

Polymorphisms in MTHFR, XRCC1 and TS are related to toxicities and disease-free survival in patients with colon cancer. The ethnic differences in frequencies of genotypes may explain the ethnic difference in toxicity profile following adjuvant FOLFOX chemotherapy.

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Acknowledgments

This research was supported by Priority Research Centers Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2009-0093820) and by Future-based Technology Development Program (Nano Fields) through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2012-0001033).

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Correspondence to Tae-You Kim.

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280_2013_2075_MOESM1_ESM.tif

Supplementary Figure 1 Inter-ethnic difference of genotype frequency. The allele and genotype frequency data of the present study were compared with those selected from publicly available sources based on International HapMap Project (http://hapmap.org/). Utah residents with northern and western European ancestry (CEU) were defined as Europids. Japanese in Tokyo (JPT) and Han Chinese in Beijing (CHB) were defined as Asians. Because the frequency data for TS (28-bp repeat in enhancer region, 6-bp deletion in 3′ UTR), AGXT 154C > T, GSTT1 (null genotype) and GSTM1 (null genotype) were lacking, ethnic frequencies of each polymorphisms were selected from previously published studies (TIFF 19173 kb).

Supplementary material 2 (DOCX 31 kb)

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Lee, KH., Chang, H.J., Han, SW. et al. Pharmacogenetic analysis of adjuvant FOLFOX for Korean patients with colon cancer. Cancer Chemother Pharmacol 71, 843–851 (2013). https://doi.org/10.1007/s00280-013-2075-3

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  • DOI: https://doi.org/10.1007/s00280-013-2075-3

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